Atherosclerosis and Vascular Biology
Atherosclerosis is a chronic, low-grade inflammation of the vessel wall, which is initiated by the loss or dysfunction of the endothelium lining the inner wall and characterised by the accumulation of lipids and the recruitment of immune cells from the peripheral blood. The proliferation and migration of vascular smooth muscle cells and production of extracellular matrix proteins ultimately results in the progressive lumen loss and stenosis, whereas the rupture of a (vulnerable) plaque may lead to platelet activation and (occlusive) thrombosis.
The research group “Atherosclerosis and Vascular Biology” examines factors and mechanisms contributing to the initiation, progression and complications of atherosclerotic lesion formation. Our analyses focus on 1) the importance of cardiovascular risk factors (in particular, obesity, smoking and hyperlipidaemia) and their modification, 2) the effects of factors produced by the adipose tissue (i.e. adipokines), and 3) the therapeutic modulation of lesion re-endothelialisation and inflammation.
Major research areas include:
- The impact of cardiovascular risk factor on the number and function of circulating immune and endothelial progenitor cells;
- The functional importance of monocytes and their subpopulations for thrombosis and ischaemia;
- The paracrine actions of adipokines, including those produced in the perivascular fat, on the integrin-mediated recruitment of proinflammatory cells and the growth of vascular lesions;
- The mechanisms and signal transduction pathways through which the adipokine leptin promotes neointima formation and atherothrombosis;The contribution of haematopoeitic progenitor cells from the bone marrow to vascular remodelling processes;
- The therapeutic modification of human endothelial progenitor cells for cell-based therapies.
In addition, the research group examines the importance of cardiac new blood vessel formation for the development of cardiac hypertrophy and heart failure (TP7, Clinical Research Unit 155).
To investigate the dynamic processes of thrombosis, fibrinolysis and re-canalisation, or the cellular and structural composition of restenotic vascular lesions, mouse models of endothelial injury and thrombosis are being used (e.g. ferric chloride or Rose Bengal model). Analyses are performed in wild-type as well as atherosclerosis-prone apolipoprotein E- and LDL-receptor-deficient mice as well as using the ob/ob and db/db mouse model of obesity and diabetes. New vessel formation is examined using the murine hindlimb ischaemia model in combination with laser Doppler perfusion imaging.
Cell lines (e.g. HUVEC, HASMC) or primary cells (e.g. smooth muscle cells, platelets, endothelial progenitor cells) and functional assays are used to study cell proliferation, migration, adhesion or angiogenesis and to confirm the findings obtained in vivo. Specific pathomechanisms are examined on the protein (immunohistochemistry, immunofluorescence, Western blot, ELISA, flow cytometry) and mRNA (PCR, in situ hybridisation) level and confirmed using signal transduction inhibitors, RNA interference, function blocking antibodies or gene transfer.
Human vascular and blood samples are also examined in order to translate findings obtained in mouse models and cells into clinically relevant pathomechanisms.
The research group is or has been funded by the German Research Foundation (DFG), the German Foundation for Heart Research (Deutsche Stiftung für Herzforschung), the Novartis Foundation for Therapeutic Research (Novartis Stiftung für Therapeutische Forschung) as well as the European Commission (Europäische Union; EUGeneHeart; FP6).
Head of working group
Research assistant, PhD student
Medical laboratory technician
Medical laboratory technician